Malheiro Rui, Diogo Luísa, Garcia Paula, Fineza Isabel, Oliveira Guiomar
Faculdade de Medicina da Universidade de Coimbra, Coimbra, Portugal.
Acta Med Port. 2012 Nov-Dec;25(6):389-98. Epub 2013 Jan 28.
Creatine deficiency syndromes are a recently described group of diseases characterized by inborn errors of creatine metabolism. Clinical features include a spectrum of neurodevelopment disorders of diverse severity. They are characterized by low levels of cerebral creatine caused by different pathogenic mutations concerning the genes coding for creatine synthesis enzymes [arginine: glicyne amidinotransferase (AGAT, EC 2.1.4.1) and guanidinoacetate methyltansferase (GAMT, EC 2.1.1.2)], AGAT and GAMT, respectively, or its transporter (CT1 deficiency), SLC6A8. Enzymatic deficiencies are transmitted as autosomal recessive traits, whereas the transporter deficit is X-linked.
To characterize the clinical and laboratorial presentation, diagnosis and treatment of cerebral creatine deficiency patients, followed in Hospital Pediátrico Carmona da Mota. The awareness of these inborn errors of metabolism as neurological disorders, namely of neurodevelopment, among the medical community is a secondary aim of the present work.
Retrospective analysis of the clinical files of patients followed in our Hospital and diagnosed with cerebral creatine deficiency syndrome.
Twelve patients belonging to seven different families were diagnosed with creatine deficiency syndromes. Five presented GAMT deficiency and seven CT1 deficiency. Present ages are 2 to 38 years old. The most common clinical presentations were: global development delay in seven patients (two with epilepsy), and speech delay in two patients. Only one patient had communication and social interaction dysfunction. In all, global development delay in the range of intellectual delay was identified. The pathognomonic pattern of cerebral creatine deficiency in the brain image was demonstrated in eight patients. Pathogenic mutations in GAMT or SLC6A8 genes were identified in all cases.
The suspicion of cerebral creatine depletion must be considered in all children presenting unexplained global psychomotor development delay. Pre-symptomatic therapy has shown promising results, especially in GAMT deficiency patients. The high rate of asymptomatic carriers of GAMT mutations in our population makes this disorder eligible to neonatal screening in Portugal.
肌酸缺乏综合征是最近描述的一组疾病，其特征为肌酸代谢的先天性缺陷。临床特征包括一系列严重程度不同的神经发育障碍。它们的特点是由于编码肌酸合成酶[精氨酸：甘氨酸脒基转移酶（AGAT，EC 2.1.4.1）和胍基乙酸甲基转移酶（GAMT，EC 2.1.1.2）]、分别为AGAT和GAMT或其转运体（CT1缺乏，SLC6A8）的基因发生不同的致病突变，导致脑内肌酸水平降低。酶缺乏以常染色体隐性性状遗传，而转运体缺陷是X连锁的。
对在儿科医院卡尔莫纳·达莫塔随访的脑肌酸缺乏患者的临床和实验室表现、诊断及治疗进行特征描述。让医学界认识到这些先天性代谢缺陷作为神经疾病，即神经发育疾病，是本研究的次要目的。
对在我院随访并诊断为脑肌酸缺乏综合征的患者临床档案进行回顾性分析。
来自七个不同家庭的12名患者被诊断为肌酸缺乏综合征。5例为GAMT缺乏，7例为CT1缺乏。目前年龄为2至38岁。最常见的临床表现为：7例患者出现全面发育迟缓（2例伴有癫痫），2例患者出现语言发育迟缓。只有1例患者有沟通和社交互动功能障碍。总体而言，确定存在智力迟缓范围内的全面发育迟缓。8例患者的脑部图像显示出脑肌酸缺乏的特征性模式。所有病例均鉴定出GAMT或SLC6A8基因的致病突变。
对于所有出现不明原因的全面精神运动发育迟缓的儿童，都必须考虑脑肌酸耗竭的可能性。症状前治疗已显示出有希望的结果，尤其是在GAMT缺乏患者中。我们人群中GAMT突变的无症状携带者比例很高，使得这种疾病在葡萄牙有资格进行新生儿筛查。
